Abstract

Obesity is a global health threat. Herein, we evaluated the underlying mechanism of anti-obese features of bitter orange (Citrus aurantium Linné, CA). Eight-week-administration of CA in high fat diet-induced obese C57BL/6 mice resulted in a significant decrease of body weight, adipose tissue weight and serum cholesterol. In further in vitro studies, we observed decreased lipid droplets in CA-treated 3T3-L1 adipocytes. Suppressed peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer binding protein alpha indicated CA-inhibited adipogenesis. Moreover, CA-treated primary cultured brown adipocytes displayed increased differentiation associated with elevation of thermogenic factors including uncoupling protein 1 and PPARγ coactivator 1 alpha as well. The effects of CA in both adipocytes were abolished in AMP-activated protein kinase alpha (AMPKα)-suppressed environments, suggesting the anti-adipogenic and pro-thermogenic actions of CA were dependent on AMPKα pathway. In conclusion, our results suggest CA as a potential anti-obese agent which regulates adipogenesis and thermogenesis via AMPKα.

Highlights

  • IntroductionObesity (body mass index, BMI > 30 kg/m2 ) has risen into a serious health threat worldwide, especially in developed countries [1]

  • Obesity has risen into a serious health threat worldwide, especially in developed countries [1]

  • high-performance liquid chromatography (HPLC) chromatogram showed that CA contains two abundant compounds, naringin and neohesperidin (Figure 1)

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Summary

Introduction

Obesity (body mass index, BMI > 30 kg/m2 ) has risen into a serious health threat worldwide, especially in developed countries [1]. According to an analytic study of 19.2 million participants from 1975 to 2014, age-standardized BMI increased from 21.7 to 24.2 kg/m2 in men and 22.1 to 24.4 kg/m2 in women globally. Speculations based on this trend expects obesity prevalence of 2025 as 18% in men and 21% in women worldwide [2]. All, when energy consumption exceeds expenditure, the surplus energy is stored as lipid, triglyceride, in white adipose tissues (WATs) [6]. While WAT works as a storage unit to save excessive energy, brown adipose tissue (BAT), on the other hand, functions in an opposite way. BAT is an organ which can dissipate energy as heat in response to cold exposure or other stimuli such as pharmacological

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